High-throughput injectability screening of high concentration protein formulations by microfluidic quartz resonators

The objective of this SBIR Direct Phase II proposal is to carry QATCH’s nanovisQ™ technology, which is a wide-shear-rate range and low volume viscometer for determining developability and injectability of biopharmaceutical formulations, from single-test sensors to high-throughput and automated format. This objective is motivated by the needs of the growing protein-based biopharmaceutical therapeutics industry (with global market size over $300 billion). Protein-based therapeutics are administered as high concentration formulations due to the volume constraints of subcutaneous injections. However, increased protein-protein interactions at these high concentrations can cause high viscosity and prevent injectability and manufacturability. Existing viscometers consume high volumes of sample, which prevents early-stage assessment and still have high protein and time costs at later stages. By developing a high-throughput, automated, wide shear rate range, low volume viscometer, protein molecules and formulations can be optimized for injectability/manufacturability earlier with less cost and risk. This proposal is significant because the proposed device can start assessing injectability of protein formulations earlier in drug development, perform this test in a higher number of formulations faster and with less material than existing technologies and consequently reduce the time and cost of R&D spent in developing new, injectable protein-based therapeutics considerably. As preliminary studies, QATCH demonstrated wide-shear-rate and low sample volume viscometers for protein formulations in single- test format. In addition, QATCH showed that 4 simultaneous measurements from 4 sensors with 9 mm spacing on the same quartz blank can be achieved accurately. As a result, the nanovisQ™ is now positioned to be a 6x4 sensor matrix and automated viscometer for high concentration protein formulations. In SBIR Phase II QATCH is proposing to 1) develop 4-sensor arrays with extended shear-rate viscosity measurements to serve high- concentration protein formulations 2) develop 6x4 sensor matrix for the high-throughput system with environmental control and the automated sample delivery capability. Developing a high-throughput and automated low-sample volume viscometer is a key step towards commercialization since low-sample volume and high-throughput are two most important parameters for drug development groups.